English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex.

MPS-Authors
/persons/resource/persons204167

Chang,  B. J.
Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons180710

Wysoczanski,  P.
Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons188023

Lee,  C. T.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons140474

Perez-Lara,  A.
Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons79056

Hofele,  R. V.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15947

Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons16093

Zweckstetter,  M.
Research Group of Protein Structure Determination using NMR, MPI for Biophysical Chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

3007166.pdf
(Publisher version), 7MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Oroz, J., Chang, B. J., Wysoczanski, P., Lee, C. T., Perez-Lara, A., Chakraborty, P., et al. (2018). Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex. Nature Communications, 9: 4532. doi:10.1038/s41467-018-06880-0.


Cite as: http://hdl.handle.net/21.11116/0000-0002-6E0A-9
Abstract
The molecular chaperone Hsp90 is critical for the maintenance of cellular homeostasis and represents a promising drug target. Despite increasing knowledge on the structure of Hsp90, the molecular basis of substrate recognition and pro-folding by Hsp90/co-chaperone complexes remains unknown. Here, we report the solution structures of human full-length Hsp90 in complex with the PPIase FKBP51, as well as the 280 kDa Hsp90/FKBP51 complex bound to the Alzheimer's disease-related protein Tau. We reveal that the FKBP51/Hsp90 complex, which synergizes to promote toxic Tau oligomers in vivo, is highly dynamic and stabilizes the extended conformation of the Hsp90 dimer resulting in decreased Hsp90 ATPase activity. Within the ternary Hsp90/FKBP51/Tau complex, Hsp90 serves as a scaffold that traps the PPIase and nucleates multiple conformations of Tau's proline-rich region next to the PPIase catalytic pocket in a phosphorylation-dependent manner. Our study defines a conceptual model for dynamic Hsp90/co-chaperone/client recognition.